Researchers shed light on MERS Coronavirus transmission

19 June 2013

Epidemiology and gene sequencing technologies have been used by researchers in the UK, the
Kingdom of Saudi Arabia, the US and Canada to show that
the novel Middle East Respiratory Syndrome (MERS) coronavirus
can spread between people in healthcare settings. The work is published in the New England Journal of Medicine today.

The scientists, from the Saudi Arabian Ministry
of Health, UCL, Wellcome Trust Sanger Institute, University of Toronto, University of Colorado and Johns
Hopkins University, rapidly investigated and defined the epidemiology,
transmission dynamics and genetic composition of the MERS-CoV cluster of 22 cases of healthcare-acquired MERS
coronavirus infections from a recent outbreak in Al-Hasa, Eastern
Province, Kingdom of Saudi Arabia.

By combining clinical monitoring techniques with state-of-the-art sequencing technology to study the outbreak, the team discovered that transmission occurs within hospitals and can be rapidly fatal.

Of the 22 people diagnosed with the coronavirus infection in
this outbreak, 65 per cent of patients have died. Until
now, little has been known about the origin and characteristics
of this deadly new virus but this work has uncovered the transmission dynamics, and clinical
and genetic characteristics of this often fatal virus.

The fact that the hospital outbreak was contained effectively and there were no more new cases reported, shows that preventive infection control measures are crucial to prevent spread of the virus.

Professor Ali Zumla, UCL Research Department of Infection

"We developed our rapid, deep, and
whole-genome sequencing of MERS coronavirus to understand more
about the genetics of this virus, and for the method to be
used in any new outbreaks. This is exactly what we have been
able to achieve," says Professor Paul Kellam from the Wellcome Trust Sanger Institute and the UCL Research Department of Infection.

The Sanger Institute team developed a deep sequencing technique that can rapidly sequence MERS coronavirus genomes.
This technique uses the miniscule levels of viral genetic material present in patients’ clinical samples taken to
diagnose the infection. Coupled to bespoke computer programs this process reduces the time of genome analysis from
weeks to days.

Using this technology, the researchers confirmed that the virus was being transmitted from person to person and the
virus accumulated limited genetic changes consistent with it replicating within a patient and then transferring to the
next. Further analysis revealed that all the coronaviruses in the outbreak came from a common ancestor that appeared
between February and April 2013. These discoveries confirmed the observations of hospital staff tracking the
transmission of the virus

"By analysing the complete genomes of four MERS-coronavirus-positive samples, we found that the
viruses were closely related to one another genetically - indicating that they are part of the same infection
outbreak," said Dr Abdullah Al-Rabeeah, Minister of Health, Kingdom of Saudi Arabia. "The
low level of sequence divergence of the virus within the Al-Hasa cluster is in concordance with the hospital
epidemiological investigation, suggesting that transmission took place within this group of patients and healthcare
workers."

Using this knowledge, clinicians have been able to minimise the spread of the infection and provide vital new
information for helping to contain future outbreaks.

"The fact that the hospital outbreak was contained effectively and there were no more new cases
reported, shows that preventive infection control measures are crucial to prevent spread of the virus," said
UCL's Professor Alimuddin Zumla who is supported
by the National Institute for Health Research University College London
Hospitals Biomedical Research Centre.

"The rapid pace with which analysis of the
cluster outbreak at Al-Hasa was initiated by the Saudi Arabian Ministry of Health, enabling rapid definition of
the epidemiology, identification of viral genome sequences and release of them for open use in the GenBank database,
helped bring the outbreak under control," continued Professor Zumla. "This reflects the true collaborative spirit and value of effective international
collaborations, which are essential to containing this virus."

Prevention of the transmission of MERS coronavirus is still a major challenge for healthcare workers. Further research
into the duration of contagiousness as well as the complete spectrum of disease is needed to help healthcare workers
develop and implement new strategies to tackle this growing issue.
Professor Ziad Memish, Deputy Minister of Health, Riyadh, Kingdom of
Saudi Arabia, said: "The Saudi Ministry of Health staff were
honoured to work with local and international world
leaders in hospital epidemiology, infectious diseases,
virology and gene sequencing experts to understand and define
the complex cluster of the novel MERS-coronavirus in the
eastern region of the Kingdom of Saudi Arabia, not just to put
local interventions to contain the outbreak, but also for
updating and evaluating existing WHO Global Infection Control
guidelines for MERS-coronavirus.

"Whilst there remain many unknowns about this new lethal virus, the Saudi Ministry of
Health is committed to continue its collaborative work with all national and international experts under the umbrella
of the World Health Organisation to unravel the mysteries of this novel virus."

The work was supported by the Kingdom of Saudi Arabia Ministry
of Health, the UCL Hospitals NHS Foundation Trust, the National Institute
for Health Research University College London Hospitals Biomedical Research
Centre, the European & Developing
Countries Clinical Trials Partnership, the US National
Institutes of Health, the European Community's Seventh Framework
Programme and the Wellcome Trust.